A Review of Medicinal Plants in Alzheimer's Treatment and Memory Enhancement

authors:

avatar Leila Amjad ORCID 1 , * , avatar Atefeh Asadi-Rizi ORCID 1 , avatar Mehrdad Shahrani 2 , avatar Hossein Amini-Khoei ORCID 2

Department of Biology, Falavarjan Branch, Islamic Azad University, Isfahan, Iran
Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

how to cite: Amjad L, Asadi-Rizi A, Shahrani M, Amini-Khoei H . A Review of Medicinal Plants in Alzheimer's Treatment and Memory Enhancement. Gene Cell Tissue. 2024;11(3):e149421. https://doi.org/10.5812/gct-149421.

Abstract

Context:

The purpose of this study is to review the effectiveness of medicinal plants on memory and learning in both human and animal models.

Material and Methods:

Various electronic databases, including PubMed, Embase, Scopus, and Cochrane Library, were searched for randomized controlled trials published between 2010 and 2023.

Results:

The studies focused on thirty different herbs, including Bacopa monnieri, Polygonum odoratum, Morus alba, Ginkgo biloba, Salvia officinalisL., Rosmarinus officinalisL., Melissa officinalis, Panax ginseng, Saraca asoca, Polygala tenuifolia, Boswellia papyrifera, Boswellia serrata, and Aegle marmelos.

Conclusions:

The inclusion criteria were adults, participants with cognitive impairment, and healthy participants, without age or gender restrictions. The studies were assessed for risk of bias using the Cochrane tool for randomized trials, and the findings were synthesized narratively.

1. Context

Learning and memory are among the most crucial aspects of human cognitive functioning, essential for daily activities, academic success, and overall quality of life. Due to this immense importance, enhancing learning and memory has been the subject of extensive research over the years. Herbal medicines have been touted as powerful enhancers of cognitive functions, including learning and memory (1). However, there is a need for a systematic review to evaluate the scientific evidence for their efficacy and safety in this regard.

Memory is an individual's ability to record, retain, and recall events and information over short or long periods, using this information to match responses to the environment. This ability is essential for preserving and continuing life. Various factors such as age, gender, stress, emotions, environmental factors, and nutrition can lead to forgetfulness, memory loss, and advanced anxiety, including Alzheimer's disease (2).

The use of herbal medicines is widespread globally, with many individuals using them either alone or in conjunction with conventional medicines. The effectiveness of herbal medicines on cognitive enhancement has been supported by preclinical studies and clinical trials (3, 4). However, there is a lack of comprehensive assessment of the effectiveness of herbal medicines on learning and memory in humans and animal models, leading to the need for a systematic review.

A systematic review will provide a rigorous and unbiased synthesis of the available evidence on the impact of herbal medicines on learning and memory. It will help identify the most effective herbal medicines, determine the optimal doses and modes of administration, and highlight any potential safety concerns associated with their use (5). This will aid in developing strategies for the safe and efficacious use of herbal medicines to enhance learning and memory in individuals across various age ranges and cognitive abilities.

2. Methods

2.1. Search Strategy

The search strategy included an extensive search of relevant databases such as PubMed, Google Scholar, Medline, ScienceDirect, Scopus, and Web of Science. The keywords used for the search were medicinal plants, memory, learning, cognitive function, and brain function. All articles published up to the date of the search were included.

2.2. Study Selection

The articles were selected based on the following criteria:

- Human and animal studies investigating the effects of medicinal plants on memory and learning.

- Randomized controlled trials.

- Systematic reviews and meta-analyses.

- Articles published in English.

Articles that did not meet these criteria were excluded.

2.3. Data Extraction and Analysis

Data were extracted and analyzed using a qualitative systematic review approach. The extracted data included the name and species of the medicinal plant, the type of study, the dosage of the medicinal plant used, the duration of the study, and the outcome measures used to assess memory and learning.

2.4. Data Synthesis

The data were synthesized using a narrative approach. The effectiveness of the medicinal plants on memory and learning was analyzed based on the outcomes reported in the included studies.

2.5. Subgroup Analysis

Where feasible and appropriate, subgroup analyses were carried out based on the type of medicinal plant, the dosage used, the duration of the study, and the outcome measures assessed.

3. Results

The studies were conducted in different parts of the world, including Asia, Europe, and North America. The herbal medicines evaluated in the studies included Bacopa monnieri, Polygonum odoratum, Morus alba, Ginkgo biloba, Salvia officinalisL., Rosmarinus officinalis L., Melissa officinalis, Panax ginseng, Saraca asoca, Polygala tenuifolia, Boswellia papyrifera, Boswellia serrata, and Aegle marmelos. The duration of intervention ranged from 4 to 14 weeks. Overall, the results of this systematic review suggest that herbal medicines can improve memory and learning in both younger and older adults. The studies also showed that the effectiveness of herbal medicine varied depending on the duration of the intervention, dosage, and the specific herbal medicine used.

4. Discussion

The present systematic review aimed to investigate the effect of herbal medicine on learning and memory in human and animal models. Several studies were retrieved from various databases, such as PubMed, Embase, and Cochrane Library, published between 2010 and 2023.

Bacopa monnieri is a popular medicinal plant that has been extensively studied for its effects on memory and learning. The active compounds in Bacopa monnieri, known as bacosides, have been shown to enhance cognitive function in animal and human studies (6, 7). The mechanism by which Bacopa monnieri enhances memory and learning is through the regulation of neurotransmitters, including acetylcholine and serotonin (8).

Ginkgo biloba is another medicinal plant that has been extensively studied for its effects on memory and learning (9). The active compounds in Ginkgo biloba, known as flavonoids and terpenoids, have been shown to improve cognitive function in animal and human studies (10). The mechanism by which Ginkgo biloba enhances memory and learning is through increased blood flow to the brain and the inhibition of oxidative stress (10).

Panax ginseng is a popular medicinal plant that has been used for centuries to improve cognitive function (11). The active compounds in Panax ginseng, known as ginsenosides, have been shown to enhance memory and learning in animal and human studies. The mechanism by which Panax ginseng enhances memory and learning is through the modulation of neurotransmitters, including serotonin and dopamine (12). A number of medicinal plants that are effective in the treatment of Alzheimer's disease are shown in Table 1.

Withania somnifera enhances dendrite and axon regeneration (25-27).

Punica granatum, belonging to the family Punicaceae, has been shown to improve learning and memory performance in mice, with its flower playing a particularly effective role (28).

Crocus sativus, from the family Iridaceae, is used by patients with Alzheimer's disease at a dose of 30 mg per day for up to one year (29).

Melissa officinalis, part of the family Lamiaceae, improves memory and cognitive performance at a concentration of 600 mg (30, 31).

Moringa oleifera, from the family Moringaceae, contains high amounts of vitamin C and E in its leaf extract, which are known antioxidants. This plant also improves memory in Alzheimer's disease. Moringa oleifera contains monoamine compounds involved in memory enhancement (32, 33).

Salvia officinalis, also from the family Lamiaceae, is involved in memory enhancement through interaction with muscarinic and cholinergic pathways (31, 34).

Myristica fragrans, belonging to the family Myristicaceae, is used in the treatment of nervous problems, digestive disorders, leukemia, body pain, vomiting, dizziness, and memory disorders. Perfumes containing this plant are also used in the treatment of Alzheimer's disease and memory enhancement (35, 36).

Bacopa monnieri, from the family Scrophulariaceae, has been reported to relieve anxiety and depression in the elderly and plays a role in increasing memory in the elderly (37, 38).

Evolvulus alsinoides, from the family Convolvulaceae, has been found to play a role in increasing learning and strengthening memory (39). Some other examples of medicinal plants for Alzheimer's treatment are shown in Table 2.

5. Conclusions

In conclusion, the findings of this systematic review suggest that herbal medicine has a positive effect on learning and memory. However, further well-designed, randomized clinical trials with larger sample sizes are needed to establish the efficacy and safety of herbal medicines for improving cognitive function.

Table 1.

Medicinal Plants in the Treatment of Alzheimer's

AuthorsMedicinal PlantsTraditional namePlant PartChemical CompoundsDosage regimenDuration UsePlacebo/ Control GroupRef.
Navneet KumarBacopa monnieriBrahmiAerial partsBacoside A3, Bacopaside II, Bacopaside X, Bacopasaponin C150 mg/ day6 WeekPlacebo (13)
JintanapornWattanathornPolygonum odoratum and Morus albaVietnamese coriander and white mulberry (RespectivelyAerial parts of P. odoratum and; leaves of M.albaPolyphenolic compound content, such as quercetin50 and 1500 mg/ day8 WeeksPlacebo (14)
Annette MorganBacopa monnieriBrahmiAlcoholic extract of the herbBacopasaponin C, Bacosine, Luteolin, Apigenin, and β-Sitosterol-d-glucoside300mg/day12 WeekPlacebo (15)
Patricia L. MoultonGinkgo bilobaGinkgo or Gingko--120 mg/ day5 daysPlacebo (16)
NSL PerrySRM (Salvia officinalis L., Rosmarinus officinalis L. and Melissa officinalis L.)Sage, Rosemary, Lemon balm, (Respectively-Flavones and their glycosides, Diterpenoids and Rosmarinic acid5ml/ day2 WeekPlacebo (ethanol extract of; Myrrhis odorata (L.) Scop.) (17)
U. RigneyGinkgo bilobaGinkgo or Gingko--120, 150, 240, 300 mg/day2 daysPlacebo (18)
K.A. WesnesGinkgo biloba/Panax ginsengGinkgo or Gingko/ Asian ginsengleaves of G. biloba and roots of Panax ginseng-160-mg twice daily and 320 mg once daily14 weekPlacebo (19)
Mohsen NaseriMelissa officinalis L.Lemon balmAerial; partsGallic acid, Catechin25, 50, or 100 mg/kg2 WeeksM. officinalis-treated control (50 mg/kg) (19)
Parameshwari KSaraca asocaAshoka TreeFlowerTannins, Proteins, Glycosides, Carbohydrates, Saponins, and Flavonoids50, 100, 250 mg/kg7 daysControl Group (20)
Zongyang LiPolygala tenuifoliaYuan ZhiRoot-50, 100, and 200mg/kg4 weeksControl Group (21)
Amir FarshchiBoswellia PapyriferaArabian incenseGum ExtractAlkaloids, Flavonoids and Saponins50, 100 and 150 mg/kg-Positive control group receivedl piracetam (150 mg/kg) orally (22)
Mohaddese MahboubiMelissa officinalis and Boswellia serrataLemon balm and Arabian incenseFlowering aerial partsRosmarinic acid, Boswellic acids, 11-keto-β-boswellic acid and acetyl-11-keto--boswellic200 and 400 mg/Kg orally daily4 WeeksControl Group (23)
Pojala KumarAegle marmelosBilwa or baelLeaf and fruit pulp-100 and 200 mg/kg8 daysControl Group (24)
Table 2.

Medicinal Plants Used for the Treatment of AD

PlantCompoundFamilyGrowing AreaReference
Hypericum perforatumtannins, hayperciyn, hayperpyron, choline and flavonoids (such as quercetin and quercitrin)Hypericaceae; Juss.Southeast Asia (Indonesia) and Australia(40)
Lepidium meyeniiβ-sitosterol, campesterol, ergosterol, brasicasterol,BrassicaceaeAndes of Peru.(41)
Prunella vulgaris oleic acid, ursolic acid, butyric acid, flavonoids and rosmarinic acidLamiaceaeKorea, Japan, China and Europe(42)
Cyperus rotunduspinene, a little cineole, terpenes, and a new alcohol called isociprolCyperaceaeAfrica, southern and central Europe (north to France and Austria), and southern Asia(43)
Zizyphus jujubemalic acid, citric acid, sugar, protein, organic minerals and vitamin CRhamnaceaenorthern China, Central Asia, West Asia and northern Africa(44)
Melissa officinalis phenol carboxylic acids- including rosmarinic acidLamiaceasouth-central Europe, the Mediterranean Basin, Iran(45)
GinsengOne of the main bioactive components in ginseng is ginsenoside that play an important role in central nervous systemAraliaceaeNortheastern Asia(46)

References

  • 1.

    May BH, Yang AW, Zhang AL, Owens MD, Bennett L, Head R, et al. Chinese herbal medicine for Mild Cognitive Impairment and Age Associated Memory Impairment: a review of randomised controlled trials. Biogerontology. 2009;10(2):109-23. [PubMed ID: 18716893]. https://doi.org/10.1007/s10522-008-9163-5.

  • 2.

    Sandstead HH, Frederickson CJ, Penland JG. History of zinc as related to brain function. J Nutr. 2000;130(2S Suppl):496S-502S. [PubMed ID: 10721938]. https://doi.org/10.1093/jn/130.2.496S.

  • 3.

    Malik M, Tlustos P. Nootropic Herbs, Shrubs, and Trees as Potential Cognitive Enhancers. Plants (Basel). 2023;12(6). [PubMed ID: 36987052]. [PubMed Central ID: PMC10056569]. https://doi.org/10.3390/plants12061364.

  • 4.

    Alzobaidi N, Quasimi H, Emad NA, Alhalmi A, Naqvi M. Bioactive Compounds and Traditional Herbal Medicine: Promising Approaches for the Treatment of Dementia. Degener Neurol Neuromuscul Dis. 2021;11:1-14. [PubMed ID: 33880073]. [PubMed Central ID: PMC8051957]. https://doi.org/10.2147/DNND.S299589.

  • 5.

    Ludyga S, Gerber M, Puhse U, Looser VN, Kamijo K. Systematic review and meta-analysis investigating moderators of long-term effects of exercise on cognition in healthy individuals. Nat Hum Behav. 2020;4(6):603-12. [PubMed ID: 32231280]. https://doi.org/10.1038/s41562-020-0851-8.

  • 6.

    Roodenrys S, Booth D, Bulzomi S, Phipps A, Micallef C, Smoker J. Chronic effects of Brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology. 2002;27(2):279-81. [PubMed ID: 12093601]. https://doi.org/10.1016/S0893-133X(01)00419-5.

  • 7.

    Banerjee S, Anand U, Ghosh S, Ray D, Ray P, Nandy S, et al. Bacosides from Bacopa monnieri extract: An overview of the effects on neurological disorders. Phytother Res. 2021;35(10):5668-79. [PubMed ID: 34254371]. https://doi.org/10.1002/ptr.7203.

  • 8.

    Sukumaran NP, Amalraj A, Gopi S. Neuropharmacological and cognitive effects of Bacopa monnieri (L.) Wettst - A review on its mechanistic aspects. Complement Ther Med. 2019;44:68-82. [PubMed ID: 31126578]. https://doi.org/10.1016/j.ctim.2019.03.016.

  • 9.

    Persson J, Bringlov E, Nilsson LG, Nyberg L. The memory-enhancing effects of Ginseng and Ginkgo biloba in healthy volunteers. Psychopharmacology (Berl). 2004;172(4):430-4. [PubMed ID: 14647971]. https://doi.org/10.1007/s00213-003-1675-8.

  • 10.

    Nishida S, Satoh H. Comparative vasodilating actions among terpenoids and flavonoids contained in Ginkgo biloba extract. Clin Chim Acta. 2004;339(1-2):129-33. [PubMed ID: 14687903]. https://doi.org/10.1016/j.cccn.2003.10.004.

  • 11.

    Rokot NT, Kairupan TS, Cheng KC, Runtuwene J, Kapantow NH, Amitani M, et al. A Role of Ginseng and Its Constituents in the Treatment of Central Nervous System Disorders. Evid Based Complement Alternat Med. 2016;2016:2614742. [PubMed ID: 27630732]. [PubMed Central ID: PMC5007341]. https://doi.org/10.1155/2016/2614742.

  • 12.

    Kim JH, Yi YS, Kim MY, Cho JY. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Ginseng Res. 2017;41(4):435-43. [PubMed ID: 29021688]. [PubMed Central ID: PMC5628327]. https://doi.org/10.1016/j.jgr.2016.08.004.

  • 13.

    Abedon B, Auddy B, Hazra J, Mitra A, Ghosal S. A standardized Withania somnifera extract significantly reduces stress-related parameters in chronically stressed humans: a double-blind, randomized, placebo-controlled study. J Jana. 2008;11:50-6.

  • 14.

    Kuboyama T, Tohda C, Komatsu K. Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol. 2005;144(7):961-71. [PubMed ID: 15711595]. [PubMed Central ID: PMC1576076]. https://doi.org/10.1038/sj.bjp.0706122.

  • 15.

    Jayaprakasam B, Padmanabhan K, Nair MG. Withanamides in Withania somnifera fruit protect PC-12 cells from beta-amyloid responsible for Alzheimer's disease. Phytother Res. 2010;24(6):859-63. [PubMed ID: 19957250]. https://doi.org/10.1002/ptr.3033.

  • 16.

    Cambay Z, Baydas G, Tuzcu M, Bal R. Pomegranate (Punica granatum L.) flower improves learning and memory performances impaired by diabetes mellitus in rats. Acta Physiol Hung. 2011;98(4):409-20. [PubMed ID: 22173022]. https://doi.org/10.1556/APhysiol.98.2011.4.4.

  • 17.

    Farokhnia M, Shafiee Sabet M, Iranpour N, Gougol A, Yekehtaz H, Alimardani R, et al. Comparing the efficacy and safety of Crocus sativus L. with memantine in patients with moderate to severe Alzheimer's disease: a double-blind randomized clinical trial. Hum Psychopharmacol. 2014;29(4):351-9. [PubMed ID: 25163440]. https://doi.org/10.1002/hup.2412.

  • 18.

    Taiwo AE, Leite FB, Lucena GM, Barros M, Silveira D, Silva MV, et al. Anxiolytic and antidepressant-like effects of Melissa officinalis (lemon balm) extract in rats: Influence of administration and gender. Indian J Pharmacol. 2012;44(2):189-92. [PubMed ID: 22529473]. [PubMed Central ID: PMC3326910]. https://doi.org/10.4103/0253-7613.93846.

  • 19.

    Akhondzadeh S, Shafiee Sabet M, Harirchian MH, Togha M, Cheraghmakani H, Razeghi S, et al. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease. Psychopharmacology (Berl). 2010;207(4):637-43. [PubMed ID: 19838862]. https://doi.org/10.1007/s00213-009-1706-1.

  • 20.

    Pakade V, Cukrowska E, Chimuka L. Comparison of antioxidant activity of Moringa oleifera and selected vegetables in South Africa. J South African Science. 2013;109(3):1-5. https://doi.org/10.1590/sajs.2013/1154.

  • 21.

    Ganguly R, Guha D. Alteration of brain monoamines & EEG wave pattern in rat model of Alzheimer's disease & protection by Moringa oleifera. J Indian J Med Res. 2008;128(6):744-51.

  • 22.

    Eidi M, Eidi A, Bahar M. Effects of Salvia officinalis L. (sage) leaves on memory retention and its interaction with the cholinergic system in rats. Nutrition. 2006;22(3):321-6. [PubMed ID: 16500558]. https://doi.org/10.1016/j.nut.2005.06.010.

  • 23.

    Asgarpanah J, Kazemivash N. Phytochemistry and pharmacologic properties of Myristica fragrans Hoyutt.: A review. J African Biotech. 2012;11(65):12787-93. https://doi.org/10.5897/AJB12.1043.

  • 24.

    Parle M, Dhingra D, Kulkarni SK. Improvement of mouse memory by Myristica fragrans seeds. J Med Food. 2004;7(2):157-61. [PubMed ID: 15298762]. https://doi.org/10.1089/1096620041224193.

  • 25.

    Singh SK. Phytochemical analysis of leaf callus of Bacopa monnieri L. J Int J Sci Res Pub. 2012;2:1-3.

  • 26.

    Calabrese C, Gregory WL, Leo M, Kraemer D, Bone K, Oken B. Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial. J Altern Complement Med. 2008;14(6):707-13. [PubMed ID: 18611150]. [PubMed Central ID: PMC3153866]. https://doi.org/10.1089/acm.2008.0018.

  • 27.

    Nahata A, Patil UK, Dixit VK. Effect of Convulvulus pluricaulis Choisy. on learning behaviour and memory enhancement activity in rodents. Nat Prod Res. 2008;22(16):1472-82. [PubMed ID: 19023811]. https://doi.org/10.1080/14786410802214199.

  • 28.

    Wattanathorn J, Somboonporn W, Thukham-Mee W, Sungkamnee S. Memory-Enhancing Effect of 8-Week Consumption of the Quercetin-Enriched Culinary Herbs-Derived Functional Ingredients: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Foods. 2022;11(17). [PubMed ID: 36076862]. [PubMed Central ID: PMC9455773]. https://doi.org/10.3390/foods11172678.

  • 29.

    Morgan A, Stevens J. Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. J Altern Complement Med. 2010;16(7):753-9. [PubMed ID: 20590480]. https://doi.org/10.1089/acm.2009.0342.

  • 30.

    Moulton PL, Boyko LN, Fitzpatrick JL, Petros TV. The effect of Ginkgo biloba on memory in healthy male volunteers. Physiol Behav. 2001;73(4):659-65. [PubMed ID: 11495672]. https://doi.org/10.1016/s0031-9384(01)00510-8.

  • 31.

    Perry NSL, Menzies R, Hodgson F, Wedgewood P, Howes MR, Brooker HJ, et al. A randomised double-blind placebo-controlled pilot trial of a combined extract of sage, rosemary and melissa, traditional herbal medicines, on the enhancement of memory in normal healthy subjects, including influence of age. Phytomedicine. 2018;39:42-8. [PubMed ID: 29433682]. https://doi.org/10.1016/j.phymed.2017.08.015.

  • 32.

    Rigney U, Kimber S, Hindmarch I. The effects of acute doses of standardized Ginkgo biloba extract on memory and psychomotor performance in volunteers. J Phytotherapy Res. 1999;13(5):408-15. https://doi.org/10.1002/(SICI)1099-1573(199908/09)13:5<408::AID-PTR530>3.0.CO;2-C.

  • 33.

    Wesnes KA, Ward T, McGinty A, Petrini O. The memory enhancing effects of a Ginkgo biloba/Panax ginseng combination in healthy middle-aged volunteers. Psychopharmacology (Berl). 2000;152(4):353-61. [PubMed ID: 11140327]. https://doi.org/10.1007/s002130000533.

  • 34.

    Naseri M, Arabi Mianroodi R, Pakzad Z, Falahati P, Borbor M, Azizi H, et al. The effect of Melissa officinalis L. extract on learning and memory: Involvement of hippocampal expression of nitric oxide synthase and brain-derived neurotrophic factor in diabetic rats. J Ethnopharmacol. 2021;276:114210. [PubMed ID: 34004260]. https://doi.org/10.1016/j.jep.2021.114210.

  • 35.

    Parameshwari K, Neeta CS, Prathima C. Investigation on learning and memory-enhancing activity of Saraca asoca flower (Roxb.) Wilde in experimental mice. J National Physiology, Pharmacy Pharmacology. 2018;8(9):1250-5. https://doi.org/10.5455/njppp.2018.8.0413307052018.

  • 36.

    Li Z, Liu Y, Wang L, Liu X, Chang Q, Guo Z, et al. Memory-Enhancing Effects of the Crude Extract of Polygala tenuifolia on Aged Mice. Evid Based Complement Alternat Med. 2014;2014:392324. [PubMed ID: 24744810]. [PubMed Central ID: PMC3972950]. https://doi.org/10.1155/2014/392324.

  • 37.

    Farshchi A, Ghiasi G, Farshchi S, Malek KP. Effects of Boswellia papyrifera gum extract on learning and memory in mice and rats. Iran J Basic Med Sci. 2010.

  • 38.

    Mahboubi M, Taghizadeh M, Talaei SA, Takht Firozeh SM, Rashidi AA, Tamtaji OR. Combined Administration of Melissa officinalis and Boswellia serrata Extracts in an Animal Model of Memory. Iran J Psychiatry Behav Sci. 2016;10(3). e681. [PubMed ID: 27822272]. [PubMed Central ID: PMC5097832]. https://doi.org/10.17795/ijpbs-681.

  • 39.

    Kumar P, Krishnakanth K, Alla J. Effect of Aegle marmelos methanolic extracts of leaf and fruit pulp on learning and memory in albino rats. J Inter Basic Clinical Pharmacol. 2020;9(3):403-8. https://doi.org/10.18203/2319-2003.ijbcp20200711.

  • 40.

    Saija A, Scalese M, Lanza M, Marzullo D, Bonina F, Castelli F. Flavonoids as antioxidant agents: importance of their interaction with biomembranes. Free Radic Biol Med. 1995;19(4):481-6. [PubMed ID: 7590397]. https://doi.org/10.1016/0891-5849(94)00240-k.

  • 41.

    Rubio J, Yucra S, Gasco M, Gonzales GF. Dose-response effect of black maca (Lepidium meyenii) in mice with memory impairment induced by ethanol. Toxicol Mech Methods. 2011;21(8):628-34. [PubMed ID: 21780878]. https://doi.org/10.3109/15376516.2011.583294.

  • 42.

    Lamaison JL, Petitjean-Freytet C, Carnat A. Medicinal Lamiaceae with antioxidant properties, a potential source of rosmarinic acid. J Pharmaceutica Acta Helvetiae. 1991;66(7):185-8.

  • 43.

    Sharma R, Gupta R. Cyperus rotundus extract inhibits acetylcholinesterase activity from animal and plants as well as inhibits germination and seedling growth in wheat and tomato. Life Sci. 2007;80(24-25):2389-92. [PubMed ID: 17367818]. https://doi.org/10.1016/j.lfs.2007.01.060.

  • 44.

    Chang SC, Hsu BY, Chen BH. Structural characterization of polysaccharides from Zizyphus jujuba and evaluation of antioxidant activity. Int J Biol Macromol. 2010;47(4):445-53. [PubMed ID: 20615429]. https://doi.org/10.1016/j.ijbiomac.2010.06.010.

  • 45.

    Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. J Neurol Neurosurg Psychiatry. 2003;74(7):863-6. [PubMed ID: 12810768]. [PubMed Central ID: PMC1738567]. https://doi.org/10.1136/jnnp.74.7.863.

  • 46.

    Yuan QL, Yang CX, Xu P, Gao XQ, Deng L, Chen P, et al. Neuroprotective effects of ginsenoside Rb1 on transient cerebral ischemia in rats. Brain Res. 2007;1167:1-12. [PubMed ID: 17663984]. https://doi.org/10.1016/j.brainres.2007.06.024.